Onco Actu du 28 juin 2019

	1. BIOLOGIE
Newly Defined Cancer Driver is Fast, Furious and Loud [University of Michigan] Researchers characterize three ways in which the gene FOXA1 mutates to trigger prostate cancer. The findings are published in Nature.
In fighting cancer, look to what other animals do [The Economist] Inspired by Peto’s paradox, as this contradiction has come to be known, researchers are exploring rates of cancer and resistance to cancer in thousands of animal species, with an emphasis on heavyweights. Their hope is to translate the animals’ cancer-fighting talents into treatments for people.
Nutritional cues regulate pancreatic tumor’s “cell drinking” [Sanford Burnham Prebys] Desperate for nutrients, rapidly growing pancreatic tumors resort to scavenging “fuel” through an alternative supply route, called macropinocytosis. Scientists are hopeful that blocking this process, often described as “cellular drinking,” could lead to tumor-starving drugs.
	1.1 BIOLOGIE - GÉNOME
Many Recurrent Cancer Mutations May Be Passengers, Not Drivers, Study Finds [Genome Web] When it came to the "mesoscale" of DNA, up to 30 base pairs around a given mutation site, the team saw an overrepresentation of APOBEC-related mutations at palindromic DNA sites, with matching sequences upstream and downstream, suggesting that the enzyme has increased activity at these sites.
Mutational "hotspots" in cancer genomes may not necessarily drive cancer growth [Mass. General Hospital] Their article published in Science describes how DNA single strands that fold back on themselves in what is called a “hairpin” structure appear highly sensitive to mutation by a gene-editing enzyme expressed in many cancers. But many of these mutation “hotspots” occur in genes that are totally unrelated to cancers, including many in noncoding areas of the genome.
	1.4 BIOLOGIE - TECHNOS
A Completely New Way to Picture DNA in Cells [In The Pipeline] Watching this technology get applied to tumor samples, to highly differentiated and organized things like neuronal tissues, to watch the effects of environmental or pharmacological stresses, et very much cetera, is going to be fun to watch!
	3.3 PRÉVENTION - VACCINS
The time is now to take a shot at eliminating six cancers caused by HPV [STAT] Insufficient vaccination is a public health threat. Our nation’s health care providers, parents, and adolescents need to take advantage of our shot to eliminate HPV-related cancers.
	3.3.2 PRÉVENTION - VACCINS (OBSERVATION)
Success of HPV vaccine could lead to end of cervical cancer [NHS Choices] Does the vaccine spell the end of cervical cancer? The results suggest it might be possible, but of course it would depend on a high level of vaccine coverage. While it may be possible in high-income countries like those included in the study, it may be more of a challenge for lower income countries.
HPV Vaccines Are Reducing Infections, Warts — and Probably Cancer [NY Times] Because it can take many years for an HPV infection to progress to cancer, the study was the first to measure precancerous lesions. It is still too early to gather rates of full-blown cancers, but lesions predict them.
	3.8 PRÉVENTION - ALIMENTATION
10 Ways to Lower the Cancer Risk of Grilling [NY Times] If you plan to grill often experts suggest taking some small steps to make a big difference in lowering your exposure to compounds that are tied to cancer.
	4.1 DÉP., DIAG. & PRONO. - PROSTATE
Prolaris® Test Accurately Predicts Risk of Metastasis in Men Diagnosed with Localized Prostate Cancer [Myriad] The large pooled analysis included 1,062 men with localized prostate cancer who were definitively treated with surgery (n=800) or radiation (n=262). The primary objective was to evaluate ability of the Prolaris test (CCP score) and the Prolaris test combined with clinical information (CCR) to predict 10-year risk of progression to metastatic disease.
	4.10 DÉP., DIAG. & PRONO. - POUMON
Risk Prediction Model May Help Determine if a Lung Nodule Will Progress to Cancer [AACR] When the risk score was applied to the replication cohort, the researchers found that the model could discriminate cancer risk with a sensitivity and specificity of 73 percent and 81 percent, respectively.
Lung cancer screening guidelines may miss more African Americans at risk [Reuters] “We need to consider not just the potential benefits, but also the potential harms, like false positive results and complications from invasive diagnostic procedures. It’s not clear how earlier initiation of screening at lower pack-year levels for African Americans would impact the benefit-to-harm ratio.”
	4.15 DÉP., DIAG. & PRONO. - IMAGERIE
One Simple Change Cut Unnecessary Imaging for Cancer Patients in Half [Penn Medicine] The researchers applied insights from behavioral economics to design a default imaging order within the EHR that specified no daily imaging during palliative radiotherapy. Default options are a type of “nudge” that present an automatic choice unless a person actively opts to make a different one.
	4.2 DÉP., DIAG. & PRONO. - GÉNOME
Molecular Profiling in Routine Practice for Advanced Cancers [ESMO] Jean-Yves Blay and ProfiLER investigators published their findings in the Annals of Oncology and concluded that molecular screening should not be used at present to guide decision-making in routine clinical practice outside of clinical trials.
Researchers criticize study calling for expansion of genetic testing for breast cancer [MedicalXpress] "Indiscriminate expanded panel testing not only has financial implications, but can lead of results that are difficult to interpret even for healthcare professionals, and may result in unnecessary surgery. Until we understand more about the genetics of breast cancer, we think it is unnecessary—and even unwise—to expand genetic testing."
	4.9 DÉP., DIAG. & PRONO. - SEIN
Biomarkers of DNA methylation can be a predictor of breast cancer risk [VUMC] Integrative analyses of genetic DNA methylation and gene expression data found that 38CpGs may affect breast cancer risk through regulating expression of 21 genes.
	5. TRAITEMENTS
Two-in-one drug combining Herceptin with chemotherapy keeps women’s breast cancers at bay [Institute of Cancer Research] Women with HER2-positive breast cancer lived for 7.6 months after starting the treatment with no disease progression, whilst those with lower HER2 levels had progression-free survival of 4.9 months, showing that the drug extended life for patients who have run out of other treatment options.
	5.12.2 IMMUNOTHÉRAPIES - CAR-T, THÉRAPIES CELLULAIRES
OncoSec Receives Exclusive Licensing Rights from Dana-Farber Cancer Institute to CAR T-Cell Therapies for the Treatment of Solid Tumor Cancers [OncoSec] Development Collaboration Will Initially Focus on CAR T-Cell Therapy for Triple-Negative Breast Cancer.
	5.12.5 IMMUNOTHÉRAPIES - PHARMA
AstraZeneca’s Imfinzi tees up small cell lung cancer fight with Roche [Fierce Pharma] If ultimately approved, Imfinzi will have a chance to compete with Roche’s rival PD-L1 inhibitor Tecentriq, which in March became the first immuno-oncology agent to get an FDA nod in first-line SCLC.
AstraZeneca gets immuno-oncology win in a disease that Merck doesn't rule [Biopharma Dive] The positive data from the CASPIAN trial puts Imfinzi several months ahead of the leading drug in its class, Merck & Co.'s Keytruda. Its trial in small cell lung cancer is expected to report data late this year.
Imfinzi improves overall survival at interim analysis in the Phase III CASPIAN trial in 1st-line extensive-stage small cell lung cancer [AstraZeneca] AstraZeneca will submit these results for presentation at a forthcoming medical meeting.
AstraZeneca challenges Roche on frontline SCLC after seizing an interim win — and Merck may not be far behind [EndPoints] The crowded playing field in the PD-1/L1 marketing game is about to get a little more complex.
	5.2 PHARMA
Innate Pharma announces publication of IPH4102 Phase I clinical trial results for CTCL in the Lancet Oncology [Innate Pharma] International IPH4102 TELLOMAK Phase II clinical trial in advanced T-cell lymphoma (TCL) launched in June 2019.
	5.2.3 PHARMA - ÉCONOMIE
ImmunoGen cuts deep to eke out cash for mirvetuximab trial [Fierce Biotech] At the end of 2018, ImmunoGen had 296 full-time staffers, 240 of whom worked in R&D, suggesting the cuts will affect around three-quarters of employees.
ImmunoGen to lay off 220 workers, as it pushes ahead with troubled drug [Biopharma Dive] ImmunoGen expects the restructuring to cut its expenses in half, allowing the biotech to stretch its $240 million in cash and equivalents to fund the business for three more years.
ImmunoGen Announces Completion of Operational Review [ImmunoGen] Company Will Prioritize Continued Development of Mirvetuximab Soravtansine and a Select Portfolio of Earlier-Stage Candidates.
Turned back at the FDA, ImmunoGen is axing 220 staffers, selling programs and hunkering down for a new PhIII gamble [EndPoints] We found out last month that the FDA had batted back their case for an accelerated approval of their antibody-drug conjugate mirvetuximab soravtansine, which had earlier failed a Phase III study for ovarian cancer. Now the other shoe is dropping.
	5.3 TRAITEMENTS - FDA, EMA, NICE...
Former FDA head Gottlieb to join Pfizer board [Biopharma Dive] While past FDA chiefs have joined drugmaker boards following their tenure, Gottlieb's move to Pfizer is both rapid and more high-profile than that of past commissioners.
Scott Gottlieb walks through the revolving door to the Pfizer board [STAT] “Philosophically, he’s returning to the ecosystem where he’s most comfortable. And he’ll get paid very well for it, too.”
Scott Gottlieb tempts the FDA's fiercest critics with his leap onto Pfizer's board of directors [EndPoints] The next chapter of Scott Gottlieb’s career will be played out in the inner sanctums of Big Pharma — forever reinforcing the FDA’s critics of the revolving door between the agency and the industry.
	5.3.4 TRAITEMENTS - AMM (FDA, EMA,...)
Janssen Announces U.S. FDA Approval of DARZALEX® (daratumumab) in Combination with Lenalidomide and Dexamethasone for Newly Diagnosed Patients with Multiple Myeloma Who Are Transplant Ineligible [Janssen] Marks the sixth DARZALEX FDA-approved use in multiple myeloma and second for newly diagnosed patients.
	5.4 TRAITEMENTS - ECONOMIE
Negotiating drug prices without restricting patient access: lessons from Germany [STAT] The German health care system achieves price moderation without the formulary exclusions, prior authorization requirements, and consumer cost sharing used by insurers in the United States.
	6. LUTTE CONTRE LES CANCERS
Guiding Cancer Control A Path to Transformation (2019) [National Academies Press] Guiding Cancer Control defines the key principles, attributes, methods, and tools needed to achieve the goal of implementing an effective national cancer control plan.
	6.9 CONTROVERSES
Potential class action lawsuit accuses the University of Chicago of sharing identifiable patient data with Google [STAT] Google and UChicago have long said that the collaboration only involved de-identified medical records and followed the federal health data privacy law known as HIPAA. The suit alleges, however, that “in reality, these records were not sufficiently anonymized and put the patients’ privacy at grave risk.”